Emerging pharmacology: inhibitors of human immunodeficiency virus integration.
The first integrase inhibitor licensed to treat HIV-1 infection was approved in late 2007, more than a decade after the introduction of the first inhibitors of the HIV-1 reverse transcriptase and protease. The unique biochemical and molecular mechanism of action of this novel class of antiretroviral drugs is the fundamental basis for their activity in treating multidrug-resistant HIV-1 infection and is important for understanding both the cellular and in vivo pharmacology and metabolism of these agents. In addition, available pharmacokinetic and drug interaction data for raltegravir and elvitegravir, the two integrase inhibitors that are the most advanced in clinical development to date, are reviewed.
Hazuda
Daria
D
Merck Research Labs, West Point, Pennsylvania 19486, USA. daria_hazuda@merck.com
Iwamoto
Marian
M
Wenning
Larissa
L
D000818:Animals; D006678:HIV / Q000187:drug effects* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008962:Models, Theoretical; D015394:Molecular Structure; D010601:Pharmacology, Clinical / Q000639:trends*; D011760:Pyrrolidinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D015363:Quinolones / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D016662:Virus Integration / Q000187:drug effects*
D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D015363:Quinolones; D000068898:Raltegravir Potassium; C509700:elvitegravir